The Startling Role of Mismatch Repair in Trinucleotide Repeat Expansions
نویسندگان
چکیده
منابع مشابه
The 26S proteasome drives trinucleotide repeat expansions
Trinucleotide repeat (TNR) expansion is the causative mutation for at least 17 inherited neurological diseases. An important question in the field is which proteins drive the expansion process. This study reports that the multi-functional protein Sem1 is a novel driver of TNR expansions in budding yeast. Mutants of SEM1 suppress up to 90% of expansions. Subsequent analysis showed that Sem1 faci...
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Human RTEL1 is an essential, multifunctional helicase that maintains telomeres, regulates homologous recombination, and helps prevent bone marrow failure. Here, we show that RTEL1 also blocks trinucleotide repeat expansions, the causal mutation for 17 neurological diseases. Increased expansion frequencies of (CTG⋅CAG) repeats occurred in human cells following knockdown of RTEL1, but not the alt...
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Expansions of DNA trinucleotide repeats cause at least 17 inherited neurodegenerative diseases, such as Huntington's disease. Expansions can occur at frequencies approaching 100% in affected families and in transgenic mice, suggesting that specific cellular proteins actively promote (favor) expansions. The inference is that expansions arise due to the presence of these promoting proteins, not t...
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To examine the genetic factors that affect the stability of disease-associated trinucleotide repeats, we have assessed the stability of CAG repeats in yeast strains with mutations in the mismatch repair system. We have found that both pms1 and msh2 mutations destabilize repeat tracts. Destabilization is evidenced both by the increased frequency of repeat length changes and in the pattern of cha...
متن کاملDNA tandem repeat instability in the Escherichia coli chromosome is stimulated by mismatch repair at an adjacent CAG·CTG trinucleotide repeat.
Approximately half the human genome is composed of repetitive DNA sequences classified into microsatellites, minisatellites, tandem repeats, and dispersed repeats. These repetitive sequences have coevolved within the genome but little is known about their potential interactions. Trinucleotide repeats (TNRs) are a subclass of microsatellites that are implicated in human disease. Expansion of CAG...
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ژورنال
عنوان ژورنال: Cells
سال: 2021
ISSN: 2073-4409
DOI: 10.3390/cells10051019